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Open research questions in Cardiac electrophysiology and arrhythmias

449 gap statements mined from Cardiac electrophysiology and arrhythmias papers in our 7.9M-paper local library, which holds 2,383 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

Choosing where to publish on Cardiac electrophysiology and arrhythmias? See the ranked Medicine journals.

What the literature leaves open

  • The lack of multi-channel modeling in the field of cardiac ion channel QSAR. The understudy of secondary channels, such as Kv7.1, Kv4.3, and Kir2.1. The absence of standardized evaluation infrastructure against which progress could be measured.

    25 Years of Cardiac Ion Channel QSAR: From hERG Dominance to Multi-Channel Modeling · 2026 · DOI

  • We have not established the methods to measure free calcium ion concentrations in HAP and therefore cannot provide such data for aficamten. We have not measured the effects of aficamten on skinned human atrial fibres. A direct study of the effects of aficamten on left ventricle muscle strips remains a task ahead.

    Contractile effects of Aficamten in the human atrium · 2026 · DOI

  • The gap identified by the paper is the lack of knowledge about the effects of Aficamten on isolated human cardiac preparations. Prior work has focused on the effects of Aficamten on animal cardiac preparations or on its binding properties to myosin.

    Contractile effects of Aficamten in the human atrium · 2026 · DOI

  • Managing arrhythmias in critically ill patients with limited cardiovascular reserve. Balancing the benefits and risks of pharmacological treatment, including the potential side effects of amiodarone. The technical challenges of catheter ablation, including the need for multiple imaging modalities.

    Editorial: Management of arrhythmias in acute and intensive care settings · 2026 · DOI

  • Further studies are needed to fully understand the pathophysiological mechanism and the interrelationship between SCD and chronic obstructive pulmonary disease (COPD). Research on the potential determining factors such as chronic systemic inflammation that occurs with advancing age and the development of several chronic diseases is needed.

    Is Lung Disease a Risk Factor for Sudden Cardiac Death? A Comparative Case–Control Histopathological Study · 2025 · DOI

  • The pathophysiological mechanism and the interrelationship between sudden cardiac death and chronic obstructive pulmonary disease is not fully known. There is a need to examine the histopathological changes in cardiac and pulmonary tissues in individuals who died from sudden cardiac death.

    Is Lung Disease a Risk Factor for Sudden Cardiac Death? A Comparative Case–Control Histopathological Study · 2025 · DOI

  • The link between a disease and sudden cardiac death remains not fully explained. The diagnostic process of channelopathies has not been fully developed. The genetic and molecular aspects of channelopathies are complex and not fully understood.

    Primary Electrical Heart Disease—Principles of Pathophysiology and Genetics · 2024 · DOI

  • Despite early characterization of mutations in selectivity filter of other Na V isoforms, little is known about the impact of DE E A on Na V 1.

    Selectivity Filter Mutation in NaV1.5 Promotes Ventricular Tachycardia · 2026 · DOI

  • The diagnostic implications of a positive epinephrine challenge for long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT) are not well understood.

    Epinephrine Challenge · 2026 · DOI

  • The clinical significance of accentuation of precordial J-point elevation during exercise in Brugada syndrome (BrS) remains unclear.

    Prevalence and Prognostic Significance of Exercise-Accentuated J-Point Elevation in Brugada Syndrome · 2026 · DOI

  • Catheter ablation has emerged as a treatment option in patients with recurrent VAs, yet the extent and reliability of its long-term benefit remain debated.

    B-6 | Meta-Analysis on Radiofrequency Ablation to Reduce Ventricular Arrhythmia in Brugada Syndrome · 2026 · DOI

  • While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored.

    Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy · 2026 · DOI

  • Parent PYRs are known to exert cardiotoxic effects by enhancing the late sodium current (I Na-L) and inducing arrhythmia, but the direct effect of 3-PBA on heart excitability has not been previously investigated.

    The Pesticide Pyrethroid Metabolite 3-Phenoxybenzoic Acid (3-PBA) Impairs Human Cardiac Nav1.5 and Action Potential Depolarization · 2026 · DOI

  • While epidemiological data consistently link urinary 3-PBA to increased cardiometabolic risk and coronary heart disease, the underlying electrophysiological mechanisms of its direct potential cardiotoxicity remain unexplored.

    The Pesticide Pyrethroid Metabolite 3-Phenoxybenzoic Acid (3-PBA) Impairs Human Cardiac Nav1.5 and Action Potential Depolarization · 2026 · DOI

  • This study was limited by the use of male mice, and the causal contribution of elevated ROS to the observed SAN dysfunction was not directly tested.

    Excess accumulation of intracellular lipid droplet impairs sinoatrial function in a mouse model of myocardial steatosis · 2026 · DOI

  • Dedicated trials are warranted to clarify causality, dose-dependency, and the therapeutic potential of microRNA-SGLT2i interactions for arrhythmia prevention and management in high-risk populations.

    Cardiac Electrophysiological Impact of Sodium Glucose Cotransporter 2 Inhibitors: A Comprehensive Review · 2026 · DOI

  • While t-tubule restoration is therefore an ideal therapeutic target, atrial t-tubule development is not well understood.

    Atrial t-tubules adopt a distinct developmental state as Ca2+ handling matures postnatally · 2026 · DOI

  • Our findings suggest that JPH2 abundance alone is insufficient to preserve T-tubule integrity in failing human hearts and challenge the role of JPH2 in human disease.

    Junctophilin-2 abundance is unaltered in human heart failure samples with disrupted T-tubules and contractility · 2026 · DOI

  • However, human-level data on JPH2's role in heart failure remain sparse, particularly regarding its protein abundance and functional relevance in human disease, which is imperative for validating therapeutic target selection.

    Junctophilin-2 abundance is unaltered in human heart failure samples with disrupted T-tubules and contractility · 2026 · DOI

  • While the transcriptional programs underlying CCS development and function have been studied within individual species, how these programs compare across species and developmental stages remains unclear.

    Conservation and divergence of transcriptional heterogeneity in the cardiac conduction system · 2026 · DOI

  • The precise electrophysiological mechanisms underlying arrhythmogenesis in HCM, particularly in the context of MYBPC3 truncating mutations, remain incompletely defined, hindering the development of targeted therapies.

    Electrophysiological remodeling in the hypertrophic cardiomyopathy MYBPC3 R943X mutant in human iPSC-derived cardiomyocytes and modulation by IKto-targeting drugs · 2026 · DOI

  • Investigating whether statistically discernible differences are associated with specific study design choices or modeling era, - Building reliable multi-channel pipelines for TdP risk…

    25 Years of Cardiac Ion Channel QSAR: From hERG Dominance to Multi-Channel Modeling · 2026 · DOI

  • Extending the model to diseased backgrounds and patient-specific hiPSC-CMs, - Investigating the impact of the complex cardiac MPS experimental configuration and conditions on the vanoxerine-induced response, - Evaluating the safety and efficacy of novel compounds using cardiac…

    Nonclinical Human Cardiac New Approach Methodologies (NAMs) Predict Vanoxerine-Induced Proarrhythmic Potential · 2025 · DOI

  • The link between a disease and sudden cardiac death remains not fully explained - The lack of the patient's clinical phenotype and poor accessibility to the patient's family history create the problem of misdiagnosis - Genetic testing should be carried out in highly specialized cardiovascular genomics centers to avoid interpretation…

    Primary Electrical Heart Disease—Principles of Pathophysiology and Genetics · 2024 · DOI

  • These findings identify myocardial steatosis as a previously underrecognized contributor to SAN dysfunction.

    Excess accumulation of intracellular lipid droplet impairs sinoatrial function in a mouse model of myocardial steatosis · 2026 · DOI

Most-cited papers in Cardiac electrophysiology and arrhythmias

Most recent work

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Open questions raised by papers listed on this page include: (1) The lack of multi-channel modeling in the field of cardiac ion channel QSAR (“25 Years of Cardiac Ion Channel QSAR: From hERG Dominance to Multi-Channel…”, 2026); (2) The gap identified by the paper is the lack of knowledge about the effects of Aficamten on isolated human cardiac preparations (“Contractile effects of Aficamten in the human atrium”, 2026); (3) Despite early characterization of mutations in selectivity filter of other Na V isoforms, little is known about the impact of DE E A on Na V 1 (“Selectivity Filter Mutation in NaV1.5 Promotes Ventricular Tachycardia”, 2026); (4) The diagnostic implications of a positive epinephrine challenge for long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT) are not well understood (“Epinephrine Challenge”, 2026); (5) The clinical significance of accentuation of precordial J-point elevation during exercise in Brugada syndrome (BrS) remains unclear (“Prevalence and Prognostic Significance of Exercise-Accentuated J-Point…”, 2026). 449 gap statements have been mined from Cardiac electrophysiology and arrhythmias papers in our 7.9M-paper local library, which holds 2,383 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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